Genetic perturbation is a powerful way to analyze the function of proteins in vivo. For this purpose, we pioneered to develop the auxin-inducible degron (AID) technology (Nishimura et al, Nat. Meth., 2009). By combining with CRISPR-based genome editing, it is now possible to generate AID conditional mutants of human cells (Natsume et al., Cell Reports, 2016; Yesbolatova et al. Methods, 2019). I would like to share the history as well as our recent improvements.