Neuroimmune Semaphorin 4A (Sema4A) is a member of Semaphorin family of transmembrane and secreted proteins.

The Semaphorin protein family members regulate the functional activity of axons in the nervous system, and Sema4A is an important regulator of neuronal and immune functions ^1,2.  In accordance to that, it was shown to be preferentially expressed on dendritic cells and B cells in the immune system ³.

Sema4A consists of an NH2-terminal signal peptide followed by a Sema domain, an Ig domain of the C2 type, a hydrophobic transmembrane region, and a cytoplasmic tail ², it has seven currently known receptors through which it mediates a complex system of intracellular and extracellular signals that regulate different physiological and pathological tissue processes ¹. 

In the nervous system, Sema4A serves as an axon guidance molecule and in the immune system it regulates immune cell activation and function, instructing the fine tuning of the immune response ¹.

Recent studies have shown a dysregulation of Sema4A expression in several types of cancer such as hepatocellular carcinoma, colorectal, and breast cancers ^1,4. The function of Sema4A in angiogenesis and cancer is not defined but it is shown to be related to the process of angiogenesis. Understanding the role of Sema4A in pathologic processes underlining tumorigenesis and tumor metastasis may guide the development of improved therapeutic treatments for cancer ¹.