PPP3CB (protein phosphatase 3 catalytic subunit beta) is a calcium-dependent, calmodulin-stimulated serine/threonine phosphatase located on chromosome 10-q22 1 that serves as a critical hub for calcium-mediated signal transduction. As the catalytic subunit of calcineurin, PPP3CB dephosphorylates key transcription factors to regulate cellular responses 2. In lysosomal homeostasis, PPP3CB dephosphorylates TFEB (transcription factor EB) in response to calcium signals, enabling its nuclear translocation and activation of lysosomal biogenesis genes 345. SMURF1 acts as a positive regulator of PPP3CB activity by promoting dissociation of its autoinhibitory domain and facilitating K63-linked ubiquitination at lysine 146, enhancing TFEB recruitment 45. PPP3CB also activates NFATC1 and inactivates ELK1 transcription factors 2. Beyond autophagy regulation, PPP3CB functions in pancreatic cancer suppression by promoting ATOH8 nuclear translocation and transcriptional inhibition of the oncogenic factor Sp1 67. Clinically, PPP3CB overexpression in neuroblastoma correlates with poor prognosis through NFAT pathway activation and c-Myc/MYCN upregulation, making calcineurin inhibitors (cyclosporin A, FK506) potential therapeutic agents 8.