PPP6R1 (protein phosphatase 6 regulatory subunit 1) is a regulatory subunit of the serine/threonine phosphatase PP6 that functions as a scaffolding component of the PP6 holoenzyme 1. The protein operates as part of a heterotrimer complex and is particularly abundant in hematopoietic cells and lymphoid tissues 1. Mechanistically, PPP6R1 participates in multiple signaling pathways. It functions redundantly with other PP6 regulatory subunits (PPP6R2 and PPP6R3) to promote RIPK1-dependent PANoptosis by enhancing pro-death S166 auto-phosphorylation of RIPK1 while reducing pro-survival S321 phosphorylation 2. Additionally, PPP6R1 interacts with Slfn2 to modulate NF-κB signaling and regulate type I interferon responses 3. The protein also associates with influenza A virus RNA-dependent RNA polymerase, supporting efficient viral replication 4. Clinically, PPP6R1 has relevance to multiple disease contexts. Mendelian randomization analysis identified PPP6R1 as causally linked to male infertility, with downregulation observed in germ cells of non-obstructive azoospermia patients, potentially influenced by endocrine-disrupting chemical exposure 5. PPP6R1 shows pleiotropic associations with cardiovascular traits 5. Copy number deletions in PPP6R1 have been identified as potential risk indicators for ventricular fibrillation during acute myocardial infarction 6. Loss of the functionally equivalent mouse ortholog SAPS1 increases radiosensitivity and impairs DNA damage responses 7, suggesting PPP6R1's role in cellular stress tolerance.