Publications

February 10, 2026

Clinical, biochemical and genetic characterization of an Egyptian patient with SRD5A3-congenital glycosylation disorder

Tawfik CA, Zaitoun R, Sabry S, Essawi ML, Elbagoury N. Ophthalmic Genet., February 10, 2026

We report a variant in the SRD3A5 gene reported for the first time in a case of CDG. We are expanding the neurophenotypic spectrum by reporting proximal limb-girdle pattern of weakness combined with diffusely brisk reflexes and bilateral extensor plantar responses suggestive of corticospinal or neuromuscular axis involvement.

February 7, 2026

Protein glycosylation and synaptic transmission: brain glycogen keeps them separated

Trentini G, Cazzanelli G, Lolli G. Brain., February 7, 2026

Brain glycogen has long been regarded uniquely as a source of energetic support in situations of emergency or heightened activity. Recently, brain glycogen was found to contain a significant amount of glucosamine, which is used to sustain protein glycosylation. In this update, we highlight that glucosamine synthesis through the hexosamine pathway would subtract glutamine, which is indispensable for glutamate and GABA recycling

February 6, 2026

Biosynthetic and genetic pathways related to sialic acid metabolism

Huang S, van de Ven EGP, Tee T, Lefeber DJ. J Biol Chem., February 6, 2026

In this review, we discuss the biosynthetic and genetic pathways in Sia metabolism with a specific focus on its role in brain, muscle, and platelets in health and genetic disease. Moreover, this review presents an overview of the clinical symptoms and genetic spectrum for each genetic disease. Overall, the molecular an biochemical profiles are not fully understood in these patients and effective therapies are limited. Therefore, additional research should focus on unravelling metabolic mechanisms that could be targeted to develop novel therapeutic strategies.

February 6, 2026

The TRAP complex (SSR1-SSR4): mechanistic roles and therapeutic opportunities

Zhang J, Wan X, Gong A. Ann Med, February 6, 2026

The TRAP complex, composed of SSR1, SSR2, SSR3, and SSR4, is essential for protein translocation, folding, and quality control, crucial for cellular balance. While individual TRAP subunits have been studied, a comprehensive understanding of their roles in human diseases is lacking. This review synthesizes current evidence on the TRAP complex and its subunits (SSR1-SSR4) to clarify their roles in tumor progression and other diseases, identify knowledge gaps, and evaluate their potential as therapeutic targets.

February 5, 2026

Feeding-regulated glycogen metabolism drives rhythmic liver protein secretion

Weger M, et al. Nat Metab., February 5, 2026

[...] Using liver microsomal proteomics, we find that proteins implicated in the early secretory pathway, such as protein glycosylation and folding in the endoplasmic reticulum (ER) and Golgi apparatus, exhibit a rhythmic expression profile, which is abolished in Bmal1-knockout mice. Mechanistically, we show that hepatic glycogenolysis provides substrates for protein N-glycosylation. In mice, perturbing hepatic glycogenolysis with pharmacological or nutritional interventions leads to ER stress and attenuates diurnal protein secretion. We confirm these results in humans, as genetic variants associated with glycogen storage disease and congenital disorders of glycosylation also alter hepatic protein secretion. Overall, our work uncovers hepatic glycogen metabolism as a circadian regulator of protein secretion.

February 5, 2026

Preferential use of alkyl-acyl phosphatidylinositol for GPI biosynthesis and diagnostic potential of lipidomics for inherited GPI deficiencies

Li X, et al. J Biol Chem., February 5, 2026

Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are attached to the cell surface via a glycolipid anchor, GPI, whose conserved core is synthesized from phosphatidylinositol (PI) in the endoplasmic reticulum through a series of enzymatic reactions. Most PI species in mammalian cells contain diacylglycerol, whereas GPI-APs predominantly possess 1-alkyl-2-acylglycerol. The basis for this characteristic lipid structure has remained unclear. Lipidomic analysis revealed that 1-alkyl-2-acyl PIs, although minor components of cellular PI, are preferentially used by GPI-N-acetylglucosaminyltransferase, which catalyzes the first step of GPI biosynthesis.

February 5, 2026

Pigmentary retinopathy, oculomotor apraxia and esotropia: a widespread and intense ocular involvement in congenital glycosylation defect

Sahan B, Rustamova N, & Sekeroglu HT. Eye., February 5, 2026

January 31, 2026

The Role of Pyridoxine Treatment for Seizures in Patients with PGAP3-Congenital Disorders of Glycosylation

Beşen Ş, Özkale Y, Sangün Ö, Erol İ. Ann Indian Acad Neuro, January 31, 2026

Hyperphosphatasia with mental retardation syndrome (HPMRS) is a rare genetic disorder characterized by developmental delay/intellectual disability, seizures, dysmorphic features, and diverse congenital anomalies with elevated alkaline phosphatase. It is an autosomal recessive disease caused by homozygous or compound heterozygous mutations in the PIGV, PIGY, PIGO, PGAP2, PIGW, and PGAP3 genes, which are involved in glycosylphosphatidylinositol biosynthesis. Mutations in the PGAP3 gene cause HPMRS type 4.

January 29, 2026

Neuro-Ophthalmic Presentation of Steroid 5a-Reductase Type 3 Congenital Disorder of Glycosylation: A Case of Monozygotic Twins

Swaroop S, Dasgupta S, Srivastava P, et al. Cureus., January 29, 2026

We report a very rare autosomal recessive metabolic disorder in monozygotic twin sisters caused by the steroid 5a-reductase type 3 (SRD5A3) gene defect, a subtype of congenital disorder of glycosylation (CDG). SRD5A3 activity is required for N-glycosylation of proteins. This step is important for the protein to gain its function. The condition is characterized by severe neurodevelopmental delay, cerebellar atrophy or hypoplasia, ocular abnormalities, and ichthyotic skin changes. We describe 20-month-old female monozygotic twins born to non-consanguineous South Asian parents.

January 28, 2026

Signal peptide peptidase (SPP)- and SPP-like 3 (SPPL3)-dependent shedding of α1,6-fucosyltransferase (FUT8) differentially affects core fucosylation

Tomida S, Kawahara R, Bienes KM, Tokoro Y, Yamasaki T, Kizuka Y. J Biol Chem. 2026 , January 28, 2026

Alpha1,6-fucosyltransferase (FUT8) biosynthesizes core fucose on N-glycans, which plays essential roles in various biological processes, including immunity and development. Although FUT8 is a Golgi-resident type II membrane protein, it is also secreted by an unknown mechanism. Here, we demonstrate that signal peptide peptidase (SPP) and signal peptide peptidase-like 3 (SPPL3), members of an intramembrane protease family, both cleave FUT8 for secretion.