RIMS1 (regulating synaptic membrane exocytosis 1) is a Rab effector protein functioning as a scaffold at the presynaptic active zone 1. It regulates neurotransmitter release probability and short-term synaptic plasticity through synaptic vesicle priming and docking 2. RIMS1 also influences dendrite formation in melanocytes and cognitive function through adipose tissue-brain axis signaling 3. Mechanistically, RIMS1 localizes to the presynaptic active zone cytoplasm and plasma membrane, where it coordinates synaptic vesicle exocytosis via small GTPase binding and protein complex assembly 1. In Drosophila, RIMS1 upregulation enhanced cognitive abilities, suggesting conserved roles in learning 3. Disease relevance is substantial and diverse. RIMS1 truncating mutations show maternal transmission bias in autism families, creating a sensitized genetic background 4. RIMS1 dysfunction associates with pediatric venous thromboembolism through rare coding variants 5. In glioblastoma, lower RIMS1 expression correlates with poorer survival and reduced immune infiltration 6. Notably, RIMS1 DNA methylation levels predict gastric cancer risk post-H. pylori eradication, with highest methylation showing 7.7-fold increased incidence 7. Clinically, a recent study identified astrocytic RIMS1 as a risk-increasing target for migraine pathogenesis through cell-type-specific analysis 1, establishing RIMS1 as a potential therapeutic target for neurological and malignant disorders.