Mezu and his younger twin brother, Gozu, were surgically altered to look like Kagen Uchiha, allowing them to take turns spying on the Uchiha clan by impersonating Kagen. Both reported directly to Danzō about their findings for several years, but in the year leading up to the Uchiha Clan Downfall, they also helped Itachi Uchiha as he tried to avert the clan's attempted coup. On the night that Itachi wiped out the Uchiha clan, Mezu was impersonating Kagen. He offered no resistance to being killed by Itachi, well aware that Kagen's body must be among the dead; he felt it was his responsibility as the older brother to die so that Gozu didn't need to.
Mezu and Gozu share similar names with another set of twins in the series, Meizu and Gōzu.