PPP1R12C encodes a regulatory subunit of protein phosphatase 1 (PP1) that controls myosin phosphatase activity through targeted dephosphorylation of myosin light chains. The protein functions by forming a holoenzyme with PP1 catalytic subunit (PP1c) and directing it to specific substrates, particularly atrial myosin light chain 2 (MLC2a) in cardiac tissue 1. In innate immunity, PPP1R12C normally associates with filamentous actin but relocates to cytoplasmic RIG-I-like receptors (RLRs) during actin cytoskeleton disturbance, enabling dephosphorylation-mediated RLR priming for antiviral responses 2. PPP1R12C is also regulated by AMPK, which phosphorylates it to promote 14-3-3 binding and enhance myosin regulatory light chain phosphorylation, playing a role in mitosis completion 3. Disease relevance is most established in atrial fibrillation (AF), where PPP1R12C expression is increased 2-fold compared to controls, leading to MLC2a hypophosphorylation and reduced atrial contractility 1. This mechanism contributes to atrial hypocontractility and increased AF susceptibility. The PPP1R12C locus (AAVS1) is commonly used as a safe harbor site for targeted gene integration in stem cell research due to its location within an active gene that permits robust transgene expression 4.