Left image: SOCE mediated by STIM1 and ORAI1 leads to Ca2+ influx, recruitment of the AKAP79/NFAT signaling complex and the phosophodiesterase PDE8. Locally recruited PDE8 reduces cAMP at ER-PM junctions. The AKAP79 signalosome recruitment is instable due to limited membrane PIP2 levels. CAN: Calcineurin. Right image: SOCE mediated by STIM1A and ORAI1 leads to reduced Ca2+ influx due to destabilized gating and hampers recruitment of PDE8. Reduced recruitment leads to reduced local cAMP degradation, which enhances PIP2 levels by activating PIPkinases. Increased levels of PIP2 stabilize the AKAP79 signalosome, enabling more efficient NFAT translocation. 