PPP1R13L (protein phosphatase 1 regulatory subunit 13 like), also known as iASPP, is a multifunctional regulator that plays a central role in apoptosis and transcription control. Mechanistically, PPP1R13L inhibits p53 and p63 transcriptional activity through direct protein-protein interaction via its Ank-SH3 domain, suppressing pro-apoptotic target gene activation 1. Additionally, PPP1R13L competes with Nrf2 for Keap1 binding to reduce reactive oxygen species levels, promoting antioxidative responses 2. The protein regulates SP1-dependent transcription and maintains a feedback loop with SP1 in response to nicotine exposure 3. PPP1R13L also functions in NF-κB-dependent negative regulation of inflammatory response [PMID:28069640 via provided context]. Disease relevance: PPP1R13L dysfunction is associated with multiple malignancies. Elevated expression drives cervical cancer progression via suppression of p63-mediated PTEN transcription and PTEN/AKT/mTOR pathway activation 1. Genetic variants interact with inflammatory genes to influence lung cancer risk 45. Conversely, biallelic loss-of-function variants in PPP1R13L cause severe pediatric dilated cardiomyopathy and arrhythmogenic cardiomyopathy, highlighting essential roles in cardiac development and desmosomal regulation 67. These distinct disease associations reflect PPP1R13L's context-dependent functions in tumor suppression versus oncogenic activity.