RIMS3 (regulating synaptic membrane exocytosis 3) is a presynaptic protein that regulates synaptic vesicle exocytosis and docking through its role as a structural component of the presynaptic active zone 1. The protein functions in calcium-regulated exocytosis and synaptic vesicle priming, coordinating neurotransmitter release at synapses 2. Beyond synaptic function, RIMS3 participates in neuronal development; related gamma-RIM isoforms regulate dendritic complexity and axonal outgrowth independent of vesicle exocytosis mechanisms 3. Clinically, RIMS3 dysfunction is implicated in neurodevelopmental disorders. De novo microdeletions encompassing RIMS3 have been identified in autism spectrum disorder patients, with coding variants (p.E177A) segregating with autism in families and predicted to be deleterious 1. RIMS3 expression is altered in schizophrenia, where increased amygdala expression of RIMS3 and related active zone proteins suggests involvement in psychiatric pathophysiology 2. Additionally, RIMS3 variants have been identified as genome-wide interaction points in tuberculosis susceptibility, linked to interferon-gamma immune responses 4. Recently, RIMS3 was identified as a diagnostic biomarker candidate in metabolic dysfunction-associated steatotic liver disease-related hepatocellular carcinoma through microbiota-host gene interactions 5.