RELM

RELM, short for resistin-like molecule, is a family of secreted cysteine-rich adipokines involved in metabolism and immune regulation. The RELM family includes several mouse proteins, notably RELMα (also called FIZZ1), RELMβ (Gob5), and RELMγ, encoded by the Retnla, Retnlb, and Retnlc genes. In humans, the closest relatives are resistin (RETN) and related RETN-like molecules, with expression patterns that differ from those seen in mice.

Expression and tissue distribution vary by member and species. In mice, RELMα is produced by adipocytes and various inflammatory cells, RELMβ is primarily secreted by goblet cells in the intestine, and RELMγ is expressed by certain immune cells such as neutrophils. In humans, resistin is mainly expressed by macrophages and adipose tissue, and the broader RELM family is not as uniformly distributed across tissues as in mice, reflecting species differences.

Biological roles attributed to RELM proteins include regulation of energy metabolism and insulin sensitivity, as well as modulation of inflammatory and immune responses. In animal models, RELMs influence glucose homeostasis and adipose tissue inflammation; their expression can be responsive to diet and obesity. They also participate in inflammatory processes in the airways and gut, contributing to tissue remodeling and cytokine production in some contexts. However, effects are often context-dependent, with reports of both pro- and anti-inflammatory actions.

Receptors and signaling pathways proposed for RELMs include CAP1 (adenylyl cyclase-associated protein 1) as a candidate, with downstream signaling involving cAMP/PKA and NF-κB pathways. The precise receptor interactions and signaling networks are active areas of research.

Clinical relevance remains exploratory. Altered RELM levels have been linked to obesity, type 2 diabetes, and inflammatory disorders in preclinical and human studies, making them subjects of interest as potential biomarkers or therapeutic targets, though no RELM-targeted therapies are approved.