Calcineurin subunit B type 1

Calcineurin subunit B type 1 (PPP3R1) is the regulatory subunit of calcineurin, a calcium-dependent protein phosphatase (UniProt: P63098). This 19.3 kDa protein confers calcium sensitivity to the calcineurin complex, enabling its phosphatase activity in response to intracellular calcium and calmodulin signaling. Calcineurin plays important roles in neuronal signaling and synaptic plasticity through dephosphorylation of key substrates.

Calcineurin has been implicated in neurodegenerative processes, particularly in calcium homeostasis dysregulation. The protein functions across multiple cellular compartments where calcium-dependent signaling occurs, including synaptic regions critical for neuronal function. Dysregulation of calcineurin activity has been associated with neuronal dysfunction in various pathological contexts.

PPP3R1 is downregulated in Alzheimer's disease brain tissue relative to age-matched controls (Chaparral AD proteomics). Human post-mortem AD brain proteomics using TMT-labeled quantification detected this protein with a mean log2 fold-change of −0.25, suggesting reduced calcineurin regulatory capacity in AD pathology. This downregulation may reflect impaired calcium-dependent signaling and phosphatase activity contributing to AD-associated neuronal dysfunction.