Basic helix-loop-helix ARNT-like protein 2 (BMAL2)

Basic helix-loop-helix ARNT-like protein 2 (BMAL2) is a transcription factor from the PAS (PER, ARNT, SIM) protein superfamily, and is structurally similar to BMAL1[2][4]. BMAL2 forms heterodimers with CLOCK or related proteins and is a core component of the molecular circadian clock, regulating transcription of genes involved in circadian rhythm, including period (PER) and cryptochrome (CRY) genes[2][5]. It binds to E-box enhancer elements in gene promoters and is crucial for the adaptive regulation of biological processes such as sleep-wake cycle, metabolic rhythms, and immune tolerance[2][3][5][6]. BMAL2 is also a regulator of immune responses in macrophages, where it upregulates PD-L1 expression, contributing to endotoxin tolerance—a process important in sepsis and immune suppression[1][5]. Pathologically, BMAL2 has been implicated in metabolic diseases, cancer (through immune checkpoint regulation), and disorders linked to circadian dysregulation[4][6]. There are no drugs currently known to directly target BMAL2, and its primary role is as a transcriptional regulator rather than a classical ‘receptor’ or enzyme.

Other names

ARNTL2BHLHE6CLIFMOP9PASD9bHLHe6CYCLE-like factorBasic-helix-loop-helix-PAS protein MOP9Brain and muscle ARNT-like 2Class E basic helix-loop-helix protein 6PAS domain-containing protein 9Member of PAS protein 9Member of PAS superfamily 9Aryl hydrocarbon receptor nuclear translocator-like protein 2Transcription factor BMAL2

Not applicable—no drugs are known to target BMAL2 directly; its activity is thought to regulate immune responses and circadian clock via gene expression and possibly those pathways are indirectly actionable.