EXD3 (exonuclease 3'-5' domain containing 3) is a nuclease enzyme that possesses 3'-5' exoribonuclease activity and is required for 3'-end trimming of AGO1-bound miRNAs. The protein demonstrates AP (apurinic/apyrimidinic) endonuclease activity, capable of incising DNA backbone at AP sites and performing exonucleolytic digestion on nicked AP sites 1. EXD3 appears to function in DNA damage response pathways, specifically involved in recovery from replication stress-induced cell cycle arrest 1. In kidney biology, EXD3 plays a functional role in podocyte integrity, with knockdown studies showing reduced nephrin gene expression in cultured human podocytes 2. Disease associations include diabetic kidney disease, where a rare missense variant (p.Asp555Asn) shows strong association with disease risk (OR=8.7) and EXD3 is downregulated in affected kidney tissue 2. The gene has also been implicated in psychiatric conditions, with genetic variants associated with suicidal ideation and behaviors 34. Additionally, EXD3 shows differential exon usage in TDP-43 proteinopathy models relevant to ALS/FTD 5, and variants are associated with hip pain 6 and gastric cancer progression 7. These findings suggest EXD3 functions in multiple biological processes including RNA processing, DNA repair, and cellular stress responses.