The GAIP-interacting protein C-terminal 1 (GIPC1) in health and disease: an update

GAIP-interacting protein C-terminal 1 (GIPC1/GIPC) is a well-established protein in the field of cancer biology. Recent studies have revealed that GIPC1 may exert opposing, context-dependent functions in various diseases or physiological processes, although the underlying regulatory mechanisms remain to be explored. Since GIPC1 contains a PDZ domain that interacts with various proteins, this domain is a promising therapeutic target. Molecular probes designed against the GIPC1-PDZ domain could therefore be valuable in developing targeted interventions. This review systematically summarizes the advances in GIPC1 research over the past decade. We discuss recent progress in understanding the roles of GIPC1 and its interacting proteins in human pathophysiology and disease, with a focus on GIPC1-interacting molecules and associated signaling pathways. Additionally, we identify key obstacles that must be overcome to realize the therapeutic potential of GIPC1. This review proposes an emerging conceptual model in which GIPC1 functions primarily as a context-dependent "signal tuner" and "trafficking gatekeeper," rather than as a simple scaffolding protein. This paradigm shift fundamentally transforms our understanding of how GIPC1 integrates diverse receptor inputs to regulate cellular behavior and highlights new directions for targeted therapeutic applications.