SIDT2 is a lysosomal membrane protein that functions as a nucleic acid transporter mediating RNA and DNA autophagy (RDA), a process involving ATP-dependent import of nucleic acids into lysosomes for degradation 12. The protein forms a tightly packed homodimer with eleven transmembrane helices and possesses a putative catalytic zinc-binding cavity capable of hydrolyzing ceramides 3. SIDT2 facilitates cellular uptake of single-stranded oligonucleotides through gymnosis and preferentially transports linear DNA over circular DNA, while binding long double-stranded RNA (500-700 bp) 4. Beyond nucleic acid transport, SIDT2 enhances gapmer antisense oligonucleotide knockdown activity and may promote endosomal escape 5. Functionally, SIDT2 participates in autophagy regulation and lipid metabolism 6. Disease relevance is emerging: biallelic SIDT2 missense variants cause progressive neurological decline with cerebellar atrophy and Parkinsonian features, with functional studies showing impaired RNA interaction and autophagy dysfunction 7. Additionally, SIDT2 mediates cancer cell apoptosis through NOX4/ROS signaling pathways activated by anticancer agents 89. SIDT2 genetic variants associate with HDL cholesterol levels, suggesting metabolic regulation roles 10.