TBC1D25 is a GTPase-activating protein (RabGAP) specific for RAB33B that regulates autophagosome maturation and vesicle trafficking. As a RAB33B effector, TBC1D25 modulates the fusion of autophagosomes with endosomes and lysosomes, critical steps in autophagy flux 1. In osteoclasts, TBC1D25 localizes to the sealing zone and ruffled membrane, where it regulates cell polarization and bone resorption 2. TBC1D25 expression is significantly altered in Paget's disease of bone osteoclasts through alternative splicing, suggesting involvement in aberrant osteoclast biology 3. Clinically, TBC1D25 has disease relevance in male infertility, with a missense variant (p.Glu50Ala) identified in an X-linked oligozoospermia family, likely impairing autophagy-dependent spermatogenesis 4. Additionally, TBC1D25 participates in influenza virus replication by modulating RAB33B-dependent autophagy, which affects viral M2 protein trafficking 1. These findings establish TBC1D25 as a key regulator of autophagy-mediated cellular processes with implications for bone metabolism, fertility, and viral pathogenesis.