SIPA1L1 (Signal-induced proliferation associated-like protein 1) is a member of the SIPA1 family of RapGAPs. SIPA1L1 was initially identified as a binding partner and degradation target of the E6 oncoprotein of high-risk papillomaviruses. Recently, it was discovered that Casein kinase I epsilon (CKIe), a Wnt-regulated kinase that regulates Wnt/b-catenin signaling, also can bind to the carboxy-terminus of SIPA1L1. CKIe phosphorylates SIPA1L1, thereby reducing its stability and alleviating its inhibition of Rap1, a protein required for Wnt8/CKIe-mediated gastrulation during embryogenesis, suggesting SIPA1L1 plays important roles in embryo development as well as control of cell proliferation.