Interferon-stimulated gene 15 protein (ISG15)

Interferon-stimulated gene 15 protein (ISG15) is a 15–17 kDa ubiquitin-like protein that is rapidly upregulated in response to type I interferons and pathogen infection[1][2][3]. ISG15 functions in two major ways: as an intracellular protein modifier (attaching covalently to target proteins in a process called ISGylation, analogous to ubiquitylation) and as a secreted cytokine participating in immune cell regulation[2][3][4]. It is involved in innate immunity, antiviral defense, regulation of interferon signaling, and modulation of protein translation and cell stress pathways[3][4]. Dysregulation or mutation of ISG15 impairs immune function, manifests as susceptibility to infectious disease and autoinflammatory syndromes, and is now recognized as an important factor in cancer biology through effects on cell signaling and stemness[1][3][6]. While no drugs are approved specifically for targeting ISG15, it is considered a key molecule in the interferon response and immune-related diseases, as well as a promising future therapeutic target in infection, inflammation, and cancer[2][3][6].

Other names

Ubiquitin-like protein ISG15Ubiquitin cross-reactive protein (UCRP)ISG15 ubiquitin-like modifier

Drugs or experimental compounds targeting ISG15 may act by: - Inhibiting ISGylation (blocking conjugation of ISG15 to target proteins) - Modulating its cytokine activity - Affecting interactions with other components of the ubiquitin-proteasome system