SEC14 and spectrin domain-containing protein 1 (SESTD1)

SEC14 and spectrin domain-containing protein 1 (SESTD1) is a multifunctional adaptor protein characterized by a SEC14-like lipid-binding domain and two C-terminal spectrin-repeat domains. SESTD1 is highly expressed in brain and other tissues, where it functions in phospholipid binding—particularly phosphatidylinositol monophosphates and diphosphates (PIP2s) in a calcium-dependent manner. SESTD1 acts as a negative regulator of dendritic spine density by modulating Rho family GTPase activity, specifically Rac1 and RhoA, through its interactions with GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs). It plays a key role in neuronal development by regulating dendrite, spine, and excitatory synapse formation in hippocampal neurons. SESTD1 also binds and serves as an adaptor for the transient receptor potential channels TRPC4 and TRPC5, potentially governing their plasma membrane localization and activity, and may participate in scaffolding interactions involving the cytoskeleton and signaling complexes. While not a direct therapeutic target, its functions place it at the intersection of membrane signaling, synaptic plasticity, and actin cytoskeleton remodeling. No drugs currently target SESTD1 directly, nor is it presently established as a disease biomarker or therapeutic target.

Other names

SEC14 and spectrin domain containing 1SESTD1SOLODKFZp434O0515SoloHuntingtin-interacting protein-like proteinProtein SoloSEC14 domain and spectrin domain-containing protein 1