SIDT1 (SID1 transmembrane family member 1) is a multipass transmembrane protein that functions as a dual-purpose transporter mediating both RNA and lipid transport. Primary Function: SIDT1 binds long double-stranded RNA (dsRNA) of 500-700 base pairs and mediates cellular uptake of exogenous dsRNA 1, with the stomach representing a major absorption site for dietary microRNAs 2. SIDT1 also localizes to endolysosomal compartments where it facilitates dsRNA transport from endocytic vesicles into the cytoplasm 3. Mechanism: N-linked glycosylation is essential for cell surface expression, RNA binding, protein stability, and RNA uptake activity 1. SIDT1 contains conserved histidine and aspartate residues coordinating zinc ions that confer ceramidase lipid hydrolytic activity, which is attenuated by cholesterol binding 4. The protein possesses conserved cholesterol recognition and accumulation (CRAC) domains required for cholesterol transport 5. Disease Relevance and Clinical Significance: SIDT1 mediates the absorption of orally-administered microRNAs with therapeutic potential—dietary miR2911 suppresses liver fibrosis in a SIDT1-dependent manner 2. SIDT1 expression is downregulated in triple-negative breast cancer, with higher expression levels associated with improved relapse-free survival and suppressed tumor growth 6. SIDT1 participates in antiviral innate immunity by facilitating dsRNA-triggered interferon responses 3, highlighting potential applications in nucleic acid therapeutics development 1.