Semaphorin 7A (Sema7A, designated CD108, previously Sema K1 or Sema L), is an ~80 kDa membrane-anchored glycoprotein that is a member of the Semaphorin family of axon guidance molecules (1 ‑ 4). On human erythrocytes, it is the John Milton Hagen (JMH) blood group antigen (4). Sema7A is the only known Class 7 or glycophosphatidylinositol (GPI)-linked semaphorin; its expression is concentrated in the brain, spleen and thymus (1 ‑ 5). Human Sema7A cDNA encodes a 44 amino acid (aa) signal sequence, a 604 aa extracellular domain (ECD) including Sema and C2‑type Ig-like domains, and an 18 aa propeptide/GPI membrane anchor signal sequence. Mature human Sema7A shares 89%, 89%, 88%, 86% and 90% aa identity with mouse, rat, canine, bovine and equine Sema7A, respectively. The Sema7A sema domain contains an RGD integrin interaction motif (4). Although it binds plexin-C1 in vitro and may be coexpressed with it, many of its activities depend on interaction with beta 1 integrins such as alpha 1 beta 1 (6 ‑ 10). Sema7A signaling through the two receptors may cause opposing effects (8). Sema7A is an immune semaphorin, with expression and activity on CD4⁺CD8⁺ thymocytes, activated T cells, macrophages and microglia (2, 9 ‑ 12). T cell Sema7A interacts with monocytic cells, stimulating their chemotaxis, production of pro-inflammatory cytokines, and dendritic differentiation (5, 6). However, on the T cells themselves, Sema7A downregulates TCR signaling by promoting TCR internalization, modulating T cell responses (9). In lung macrophages, Sema7A is induced by TGF-beta and participates in TGF-beta -induced lung fibrosis (12). Sema7A is also expressed on pre-osteoblasts and osteoclasts, where it promotes migration and fusion, respectively; on keratinocytes, where it promotes melanocyte spreading and dendricity; and on some neurons, for example, promoting axon outgrowth in the developing olfactory tract (8, 10, 13).