Semaphorin 4D (Sema4D) has been suggested to be upregulated in stressed or damaged neurons and signal through plexin-B1/B2 receptors to activate glial cells and endothelial cells, contributing to the development of neurodegenerative diseases.545 In May 2020, pepinemab, a monoclonal antibody to Sema4D has been registered in a Phase I/II clinical trial by Vaccinex for the treatment of AD (clinicaltrials.gov). This evidence concerns the gene SEMA4D and neurodegenerative disease.