Bmal1, also known as Brain and muscle arnt-like protein 1, is a crucial transcription factor that is a core component of the circadian oscillation machinery. It forms a heterodimer with Clock and binds to the E-box element in the promoters of genes like Period circadian protein (Per) and Cryptochrome (Cry), regulating the rhythmic expression of circadian clock control genes. Bmal1 is involved in multiple biological processes, with its dysregulation associated with various diseases [4].

In diabetic cardiomyopathy, Bmal1 downregulation in cardiomyocyte-specific knockout mice (CKB) and type 2 diabetes (T2D) mice accelerates cardiac hypertrophy and diastolic dysfunction, while overexpression ameliorates these pathological changes. Bmal1 seems to act through the Bcl2/IP3R-mediated mitochondrial Ca2+ overload pathway [1].

In sepsis-induced acute lung injury, BMAL1 deficiency in macrophages exacerbates systemic inflammation and lung injury by upregulating CXCL2 expression, which increases neutrophil recruitment and NETs formation via binding to CXCR2 [2].

In sepsis-induced acute kidney injury (AKI), decreased BMAL1 expression is observed, and its overexpression alleviates renal tubular injury by reducing ferroptosis levels in renal tubular epithelial cells through inhibiting YAP expression and the Hippo pathway [3].

In conclusion, Bmal1 plays a vital role in maintaining normal physiological functions, especially in regulating circadian rhythms. Its dysregulation is associated with multiple diseases such as diabetic cardiomyopathy, sepsis-related organ injuries. Gene knockout mouse models, like CKB for Bmal1, have been instrumental in revealing its role in these disease conditions, providing potential therapeutic targets for treatment.