CRY1

CRY1 (cryptochrome 1) is a core circadian clock repressor, and CRY1/2 repress CLOCK:BMAL1 transcription while interacting with nuclear receptors that regulate metabolism^[1][2]. Mechanistically, the CRY1 tail, especially the exon 11 region, controls circadian timing by regulating CRY1 association with CLOCK:BMAL1^[3]. In disease models, a human CRY1 variant causes familial delayed sleep phase disorder, linking altered CRY1 repression to delayed circadian timing^[4]. In cancer models, DNA damage stabilizes CRY1, and stabilized CRY1 promotes homologous recombination gene expression, DNA repair, and cell survival^[5]. Compared with CRY2, CRY1 shows redundant and distinct functions; isoform-selective studies found KL101 stabilizes CRY1, whereas TH301 stabilizes CRY2^[7]. For experimental applications, KL001 prevents ubiquitin-dependent CRY degradation and lengthens circadian period, while KL201 selectively stabilizes CRY1 and supports isoform-specific circadian clock research^[6][8].