HUWE₁ is a HECT-domain ubiquitin E3 ligase that plays numerous roles in cellular processes by promoting degradation of its substrates. Although it has been discovered that mutations in HUWE₁ can lead to countless cancers or human diseases, given a number of the substrates with various cellular functions, the in vivo role of HUWE₁ remains elusive. Importantly, conventional HUWE₁ gene knockout (KO) leads to embryonic lethality, which makes it difficult to analyze the role of HUWE₁ in different tissues and organs. Here, we created whole body inducible HUWE₁ knockout mice, in which HUWE₁ was acutely deleted in 4-week-old mice. We show that inducible HUWE₁ KO did not result in lethality, and we will discuss the phenotypes of the KO mice.