RELT-like protein 2 (RELL2)

RELT-like protein 2 (RELL2) is a type I transmembrane protein, classified as a member of the tumor necrosis factor receptor superfamily (TNFRSF)-like family. RELL2 is predominantly expressed in hematopoietic tissues (thymus, spleen) as well as immune-privileged sites (testis, brain, placenta), and is structurally related to RELT and RELL1, with which it can form complexes at the plasma membrane. It lacks the canonical TNFR extracellular cysteine-rich domains and instead carries a short extracellular sequence and a disordered C-terminal region. Functional studies implicate RELL2 in promoting apoptosis, particularly through activation of the p38 MAPK stress pathway, and suggest a role in the regulation of cell survival and the immune response. RELL2 may act as a protective factor in some cancers, such as esophageal squamous cell carcinoma, by promoting apoptosis, and is considered a putative immune biomarker in pan-cancer analyses. However, its exact physiological ligand, mechanisms of signaling, and clinical significance remain under investigation.

Other names

C5orf16RELT like 2RELL2RELT-like protein 2UNQ9423/PRO34565FLJ90583receptor expressed in lymphoid tissues like 2

Not established for approved drugs; upregulation of RELL2 can activate the MAPK14/p38 pathway leading to apoptotic cell death (demonstrated in overexpression or small molecule experimental contexts such as with Polyphyllin VI)