RanBP-type and C3HC4-type zinc finger-containing protein 1 (RBCK1)

RanBP-type and C3HC4-type zinc finger-containing protein 1 (RBCK1, also known as HOIL-1) is an enzyme classified as an E3 ubiquitin-protein ligase, essential for protein ubiquitination processes and a critical component of the linear ubiquitin chain assembly complex (LUBAC)[3][5]. It regulates protein degradation and stability—particularly through the addition of linear (Met1-linked) ubiquitin chains—and contributes to NF-κB pathway activation and innate immune responses[3][4][5]. RBCK1 plays important roles in cell survival, proliferation, migration, and inflammation, and its dysregulation is implicated in cancer progression (e.g., breast and liver cancers), immunodeficiency, autoinflammatory syndromes, and congenital myopathy[1][2][4]. Targeting RBCK1 or its complex may have therapeutic promise, but may also pose challenges due to its broad roles in immunity and cell homeostasis.

Other names

HOIL-1Heme-oxidized IRP2 ubiquitin ligase 1RING finger protein 54Hepatitis B virus X-associated protein 4Ubiquitin-conjugating enzyme 7-interacting protein 3C20orf18RNF54UBCE7IP3XAP3XAP4PBMEIPGBM1RBCK2ZRANB4

Drugs targeting RBCK1 would likely act by modulating ubiquitination activity, disrupting LUBAC complex function, or affecting NF-κB signaling[1][2][3].