RHAMM

RHAMM, short for Receptor for Hyaluronan-Mediated Motility, is a protein encoded by the human HMMR gene. It is also known as CD168 and Hyaluronic Acid Receptor for Motility. Unlike classical cell surface receptors, RHAMM lacks a signal peptide and a transmembrane domain; it is found inside cells in the cytoplasm and nucleus and can appear on the cell surface in certain contexts, often in cooperation with other hyaluronan receptors such as CD44.

RHAMM mediates cellular responses to hyaluronan (HA), a major component of the extracellular matrix. It promotes HA-dependent cell migration and is involved in wound healing and tissue remodeling. During cell division, RHAMM localizes to the centrosome and mitotic spindle, where it contributes to spindle assembly, chromosome alignment, and regulation of cell proliferation. These roles tie its function to both motility and cell cycle control.

In signaling terms, RHAMM can activate pathways such as ERK1/2 and JNK in response to HA, influencing cytoskeletal dynamics and motility. It can operate in concert with CD44 to transduce HA signals, though RHAMM also has HA-independent activities that affect cell behavior and cytoskeletal organization.

Clinical relevance of RHAMM has grown with findings of its upregulation in several cancer types, where high RHAMM expression has been associated with invasive features and, in some studies, poorer prognosis. Experimental reduction of RHAMM expression or function can diminish migratory and metastatic capabilities in model systems, highlighting its potential as a therapeutic target or biomarker. The protein exists in multiple isoforms produced by alternative splicing, and its localization and function are modulated by post-translational modifications and interactions with microtubules and other cytoskeletal regulators.