Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca2+-mediated signals (PubMed:15671020, PubMed:18838687, PubMed:19154138, PubMed:23468591). Many of the substrates contain a PxIxIT motif and/or a LxVP motif (PubMed:17498738, PubMed:17502104, PubMed:23468591, PubMed:27974827, PubMed:22343722). In response to increased Ca2+ levels, dephosphorylates and activates phosphatase SSH1 which results in cofilin dephosphorylation (PubMed:15671020). In response to increased Ca2+ levels following mitochondrial depolarization, dephosphorylates DNM1L inducing DNM1L translocation to the mitochondrion (PubMed:18838687). Dephosphorylates heat shock protein HSPB1 (By similarity). Dephosphorylates and activates transcription factor NFATC1 (PubMed:19154138). In response to increased Ca2+ levels, regulates NFAT-mediated transcription probably by dephosphorylating NFAT and promoting its nuclear translocation (PubMed:26248042). Dephosphorylates and inactivates transcription factor ELK1 (PubMed:19154138). Dephosphorylates DARPP32 (PubMed:19154138). May dephosphorylate CRTC2 at 'Ser-171' resulting in CRTC2 dissociation from 14-3-3 proteins (PubMed:30611118). Dephosphorylates transcription factor TFEB at 'Ser-211' following Coxsackievirus B3 infection, promoting nuclear translocation (PubMed:33691586).