Consistent with this observation, and in contrast to other HER receptors for which genetic alterations are widely linked to oncogenesis (Arteaga and Engelman, 2014), HER4 is more commonly observed to be lost or downregulated in human cancers (Muraoka-Cook et al., 2008; Arteaga and Engelman, 2014; Naresh et al., 2006; Segers et al., 2020). This evidence concerns the gene ERBB4 and cancer.