KICSTOR complex protein SZT2 (SZT2)

KICSTOR complex protein SZT2 (abbreviated as SZT2) is a large, conserved protein forming a critical component of the KICSTOR complex, which acts as a negative regulator of the mechanistic target of rapamycin complex 1 (mTORC1) signaling in response to amino acid deprivation[1][3][4]. SZT2 is predominantly expressed in the central nervous system and is implicated in the regulation of autophagy, ciliogenesis, and neuronal development[1][2]. Mutations in SZT2 are linked to severe neurodevelopmental and epileptic disorders, including early-onset epilepsy, developmental delay/intellectual disability, and macrocephaly (DEE18/EIEE18)[1][2]. Biochemically, it functions upstream of the RAG GTPases, necessary for negative regulation of mTORC1 in low amino acid conditions; loss of SZT2 leads to persistent activation of mTORC1, which is reversible by specific mTORC1 inhibitors (e.g., rapamycin). SZT2 is not currently a direct therapeutic target, and there are no approved drugs specifically targeting it, though experimental studies use mTORC1 pathway inhibitors to investigate its biological functions and rescue disease phenotypes[1][4].

Other names

SZT2C1orf84KIAA0467FLJ10387SZT2BRP11-506B15.1FLJ34502SZT2AKICS1seizure threshold 2 protein homologseizure threshold 2 homolog A (mouse)seizure threshold 2 homolog B (mouse)DEE18EIEE18

In experimental settings, mTORC1 inhibitors act by inhibiting over-activated mTORC1 signaling resulting from SZT2 deficiency