It is incontrovertible that transgenic hACE2 models, particularly the K18-hACE2 model, have provided a better understanding of the pathogenesis of COVID-19 yet the one notable and consistent drawback of many of these models is the ability of virus to infect, efficiently replicate, and spread within the parenchyma, which contributes to increased mortality. The gene discussed is KRT18; the disease is COVID-19.