Arguably, the best-understood examples of human diseases related to PIP-induced protein recruitment and conformational changes are activating mutations in class IA PI3K in cancer (12, 105, 106), in PI3KCA-related overgrowth spectrum, and in activated PI3K-delta syndrome (APDS), a primary immunodeficiency disorder (107). This evidence concerns the gene PIK3CA and activated PI3K-delta syndrome.