POMK (protein O-mannose kinase) is a glycan-specific kinase that catalyzes phosphorylation at the 6-position of O-mannose within the trisaccharide GalNAc-β3-GlcNAc-β4-mannose on α-dystroglycan 1. This phosphorylated O-mannosyl structure is essential for high-affinity binding of α-dystroglycan to laminin G-domain-containing extracellular matrix proteins [UniProt data supported by 26]. POMK localizes predominantly to the cis/medial-Golgi apparatus and functions within a sequential glycosylation pathway involving POMGNT2, B3GalNT2, and downstream glycosyltransferases 3. The kinase possesses a unique active site architecture with non-canonical residue positioning and disulfide bridge stabilization, recognizing substrates through specific GalNAc-β3-GlcNAc interactions 1. Biallelic POMK mutations cause alpha-dystroglycanopathies, including Walker-Warburg syndrome and limb-girdle muscular dystrophy with congenital brain and eye anomalies 45. These conditions manifest as progressive muscular weakness with severe CNS malformations due to impaired extracellular matrix composition and satellite cell dysfunction 6. Additionally, altered POMK expression has been identified in various human cancers, where overexpression contributes to pro-oncogenic signaling through dysregulated dystroglycan glycosylation 7.