Huntingtin protein (Htt), whose mutation causes Huntington's disease (HD), interacts with large numbers of proteins that participate in diverse cellular pathways. This observation indicates that wild-type Htt is involved in various cellular processes and that the mutated Htt alters these processes in HD. The roles of these interacting proteins in HD pathogenesis remain largely unknown. In the present review, we present evidence that Htt-interacting protein 1 (HIP-1), an endocytic protein, together with its interacting partner HIPPI, regulates apoptosis and gene expression, both processes being implicated in HD. Further studies are necessary to establish whether the HIPPI-HIP-1 complex or other interacting partners of HIPPI regulate apoptosis and gene expression that are relevant to HD.