TBP and spinocerebellar ataxia type 17: It is perhaps not surprising that evidence from animal models suggests that TBP mutation contributes to SCA17 progression in 2 ways as follows: (1) through toxic gain-of-function, resulting in protein misfolding and neural cell death, and (2) through loss-of-function of endogenous TBP (Nakamura et al. 2001; Hsu et al. 2014; Toyoshima and Takahashi 2018; Liu et al. 2019).