SEC22C is an endoplasmic reticulum (ER)-localized transmembrane protein functioning as a v-SNARE involved in vesicle trafficking between the ER and Golgi apparatus 1. The protein exists in multiple isoforms generated by alternative splicing that alter C-terminal transmembrane domain (TMD) numbers, enabling dynamic subcellular localization regulation 2. Isoforms with four TMDs localize to the cis-Golgi through an ARF4-dependent mechanism, while those with fewer TMDs remain ER-resident, allowing SEC22C to function at both compartments 2. As a SNARE protein, SEC22C participates in membrane fusion processes essential for secretory transport and regulates SNARE complex organization, as evidenced by its effects on syntaxin 5 and BET1 localization patterns 1. SEC22C represents one of multiple mammalian SEC22 homologs with specialized roles in the elaborate ER-Golgi transport machinery 1. While SEC22B alterations are implicated in human cancers and diseases, specific disease associations for SEC22C remain poorly characterized 3. The splicing-dependent localization mechanism suggests SEC22C may serve specialized functions in different cellular compartments, though additional research is needed to elucidate its precise pathophysiological role.