Il36g, also known as interleukin 36 gamma, is a cytokine that plays a role in inflammatory responses and immune-related processes. It is associated with pathways such as the IL-23/IL-17 axis which is crucial in psoriasis pathology [5]. Genetic studies on its variants can provide insights into its function in diseases.

In psoriasis, several key findings related to Il36g have emerged. Its expression pattern in keratinocytes is inversely related to that of PCSK9, with Il36g expression highest in granular layer keratinocytes [1]. Genetic variants of Il36g are associated with psoriasis susceptibility, severity, and joint involvement. For example, the G allele of the IL36G rs7584409 variant shows a protective effect against psoriasis, but in patients with psoriasis, it is associated with moderate-to-severe disease and psoriatic arthritis [4]. In addition, single-cell and spatial sequencing indicate that SFRP2+ fibroblasts can activate Il36G in keratinocytes, amplifying inflammatory responses in psoriasis [3].

In cancer, IL36G-producing neutrophil-like monocytes, called cachexia-inducible monocytes (CiMs), promote skeletal muscle loss in cachexia, and genetic inhibition of IL36G-mediated signaling attenuates this effect [2].

In conclusion, Il36g is significantly involved in inflammatory and immune-related processes, especially in psoriasis and cancer-associated cachexia. Genetic studies and in-vivo functional studies, such as those exploring the effects of Il36g genetic variants in human populations and the impact of genetic inhibition of Il36G-mediated signaling in cancer models, have provided important insights into its role in these disease conditions.