SYT2 encodes synaptotagmin-2, a calcium-dependent phospholipid-binding protein that functions as a calcium ion sensor at the synaptic vesicle membrane 1. The protein plays a critical regulatory role in neuromuscular junction (NMJ) transmission, mediating calcium-dependent activation of synaptic vesicle fusion and exocytosis 1. SYT2 exhibits calcium-dependent binding to inositol polyphosphates and phospholipids, with particular importance of its C2B domain for protein function 2. The protein is also involved in vesicle-mediated transport and SNARE complex interactions during synaptic vesicle trafficking at the active zone 1. Pathogenic variants in SYT2 cause congenital myasthenic syndromes (CMS) types 7A and 7B, characterized by impaired neuromuscular signal transmission 1. SYT2-related disease presents with distal muscle atrophy, foot deformities, and in severe cases, neonatal hypotonia with weak cry 2. Most disease-associated mutations localize to the C2B domain 2. Electrophysiological findings include reduced compound muscle action potentials and incremental responses characteristic of presynaptic dysfunction 2. SYT2-related motor neuropathy should be suspected in patients presenting with presynaptic NMJ dysfunction combined with predominantly distal motor neuropathy, particularly with positive family history 3. The disease follows both autosomal recessive and dominant inheritance patterns 4.