EXD1 (exonuclease 3'-5' domain containing 1) is an RNA-binding component of the PET complex essential for piRNA biogenesis during spermatogenesis. Despite containing an exonuclease domain, EXD1 functions as an inactive exonuclease and likely acts as an RNA adapter within the complex 1. The PET complex processes piRNAs, which are small regulatory RNAs that form complexes with Piwi proteins to silence transposable elements through transcriptional and post-transcriptional mechanisms, thereby maintaining germline integrity 1. EXD1 specifically participates in secondary piRNA biogenesis by facilitating PIWIL2 slicing-triggered loading of PIWIL4 piRNAs 1. Clinically, EXD1 variants are associated with male infertility. The first documented loss-of-function EXD1 variant (c.550C>T, p.R184*) was identified in a patient with oligoasthenoteratozoospermia characterized by acrosomal hypoplasia 1. Notably, intracytoplasmic sperm injection (ICSI) treatment in this patient resulted in live birth, suggesting therapeutic potential 1. This discovery broadens the piRNA-related genetic spectrum of male infertility and provides a foundation for genetic counseling and potential clinical management strategies for affected individuals 1.