Synaptotagmin-like protein 2 (SYTL2) belongs to the synaptotagmin-like protein family, which contains a N-terminal RabBD (Rab-binding) domain and two C-terminal C2 domains. RabBD domain mediates interaction with RAB27A and recruitment on to vesicular structures in cytotoxic T-lymphocytes (CTL) [, ]. The C2 domain mediates binding to phosphatidylserine (PS) and phosphatidylinositol 4,5-bisphosphate (PIP2) and localisation to the cell membrane [, ]. SYTL2 has several isoforms produced by alternative splicing, and different isoforms may have different functions.In humans, SYTL2 isoform 1 acts as a RAB27A effector protein and plays a role in cytotoxic granule exocytosis in lymphocytes. It is required for cytotoxic granule docking at the immunologic synapse. Isoform 4 binds phosphatidylserine (PS) and phosphatidylinositol-4,5-bisphosphate (PIP2) and promotes the recruitment of glucagon-containing granules to the cell membrane in pancreatic alpha cells. Its binding to PS is inhibited by Ca2+ while binding to PIP2 is Ca2+ insensitive [, , ]. In mice, SYTL2 isoform 1 may play a role in melanosome transport and vesicle trafficking. It controls melanosome distribution in the cell periphery and regulates melanocyte morphology [, ]. Isoform 1 also acts as a positive mediator of mucus secretion by the surface mucus cells of the stomach. It mediates basal mucus secretion by gastric surface cells by promoting the proper granule biognesis and docking of mucus granules with the apical plasma membrane []. Isoform 11 acts as a RAB27A effector protein and plays a role in cytotoxic granule exocytosis in lymphocytes. It is required for cytotoxic granule docking at the immunologic synapse. Isoform 1 may play a role in melanosome transport and vesicle trafficking. It controls melanosome distribution in the cell periphery and regulates melanocyte morphology.
