Cryptochrome 2 stabilization alleviates psoriasis by inhibiting keratinocyte hyperproliferation and inflammation

Psoriasis, a chronic inflammatory skin disorder, is characterized by aberrant keratinocyte proliferation and immune dysregulation. Although cryptochrome 2 (CRY2), a circadian rhythm regulator, has been implicated in inflammatory conditions, its role in the psoriasis pathogenesis remains elusive. Here, we report a marked downregulation of CRY2 expression in psoriasis, which was reversed upon biological therapy, suggesting its pivotal involvement in disease progression. Using cellular, murine, and in vitro human tissue models, we revealed that CRY2 deficiency exacerbates inflammatory and hyperproliferative responses via ERK1/2 signaling activation. Furthermore，pharmacological stabilization of CRY2 using KL001 significantly ameliorated core psoriatic phenotypes, including epidermal thickening, proliferation marker expression, and chemokine production. These findings underscore CRY2 as a compelling therapeutic target in psoriasis, with KL001-mediated modulation offering potential as an adjunctive treatment strategy.