{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Human germinal center‐associated lymphoma (HGAL), also known as GCSAM, is a germinal center–specific adaptor protein that plays a multifaceted role in normal B‐cell physiology and lymphomagenesis. HGAL is predominantly expressed in germinal center B cells and in lymphomas derived from these cells, and its expression is associated with improved clinical outcome. Functionally, HGAL modulates B‐cell receptor (BCR) signaling by directly binding to and enhancing the kinase activity of Syk as well as interacting with downstream effectors such as Grb2, thereby fine‐tuning antigen‐driven signaling processes in B cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In parallel, HGAL influences cytoskeletal dynamics by directly interacting with actin and myosin; such interactions not only potentiate binding between myosin and F‐actin but also reduce the maximal velocity of myosin‐driven actin translocation, resulting in decreased lymphocyte motility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, HGAL further limits cell motility by enhancing activation of RhoA through direct binding to the catalytic domains of RhoA‐specific guanine nucleotide exchange factors, an effect that contributes to the confinement of germinal center B cells and appears to limit lymphoma dissemination."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": " Finally, post‐translational modifications such as phosphorylation, myristoylation, and palmitoylation regulate HGAL’s intracellular trafficking and its recruitment to membrane microdomains, thereby modulating its effects on BCR signaling and cell motility in a context‐dependent manner."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Collectively, these mechanisms not only ensure proper germinal center function but also restrain lymphoma cell dissemination, which contributes to the favorable prognosis observed in HGAL‐expressing diffuse large B‐cell and classical Hodgkin lymphomas."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Isabel Romero-Camarero, Xiaoyu Jiang, Yasodha Natkunam, et al. 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