NLRP14 is a NOD-like receptor family member with critical roles in both oocyte maturation and spermatogenesis, functioning through noncanonical mechanisms distinct from traditional inflammasome signaling. In female reproduction, NLRP14 is preferentially expressed in oocytes and early embryos, where it acts as a cytoplasmic-specific regulator of UHRF1 stability 1. NLRP14 protects UHRF1 from proteasome-mediated degradation and prevents its nuclear translocation, maintaining proper oocyte competence during cytoplasmic and nuclear maturation 1. Additionally, NLRP14 regulates calcium homeostasis by stabilizing the mitochondrial Na+/Ca2+ exchanger NCLX through K27-linked ubiquitination control, which is essential for sustaining Ca2+ oscillations required for embryonic development 2. In spermatogenesis, NLRP14 promotes spermatogonial stem cell differentiation and meiosis by forming the NLRP14-HSPA2-BAG2 complex, which protects HSPA2 from polyubiquitination and promotes its nuclear translocation 3. Furthermore, NLRP14 negatively regulates cytosolic nucleic acid sensing by targeting TBK1 for ubiquitination and degradation, preventing inappropriate immune activation during fertilization 4. Loss-of-function NLRP14 variants cause female infertility with oocyte maturation defects and early embryonic arrest, and male infertility with oligozoospermia, establishing NLRP14 as a critical maternal effect and germline factor 13.