PPP3R1 encodes the regulatory subunit B (calcineurin B) of calcineurin, a calcium-dependent protein phosphatase that plays critical roles in cellular signaling and homeostasis 1. As a calcium-binding regulatory subunit, PPP3R1 forms a heterodimer with catalytic subunits to create the functional calcineurin enzyme complex 1. The protein is essential for sleep regulation, where calcineurin functions as a sleep-promoting phosphatase at excitatory post-synapses, competing with wake-promoting PKA signaling 2. In disease contexts, PPP3R1 shows tissue-specific protective effects during pancreatitis, with pancreatic calcineurin promoting local inflammation while hematopoietic calcineurin contributes to lung inflammation 3. The protein undergoes post-translational regulation through ubiquitination by SMURF1, which enhances TFEB recruitment and promotes lysosomal homeostasis following cellular damage 4. PPP3R1 is downregulated in hypercholesterolemic hearts through microRNA-mediated mechanisms, contributing to cardiac dysfunction 5. Recent studies identify PPP3R1 as a potential therapeutic target for systemic lupus erythematosus, with drugs like voclosporin and cyclosporine targeting the calcineurin pathway 6. The gene maps to chromosome 2-p16 and represents a promising target for various neurological and autoimmune disorders 7.