HERV-K(HML2) elements belong to betaretroviruses, and full-length proviruses encode the canonical retroviral Gag, Pro (protease), Pol (polymerase), and Env (envelope) proteins, as well as Rec, an accessory protein whose functions are similar to those of Rem in mouse mammary tumor virus or Rev in human immunodeficiency virus (HIV). Some of these proviruses are expressed and produce viral particles in tumor-derived cell lines. Functional assays showed that among the six complete Env ORFs identified in the human databases, one corresponds to a functional protein able to confer infectivity to heterologous retroviral particles.