Thg-1pit (Tsc22d4), a murine gene belonging to the TGF-beta1-stimulated clone 22 domain (TSC22D) family, is expressed in developing and adult cerebellar granule neurons and mature Purkinje cells. We have studied THG-1pit function in primary cultures of mouse cerebellar granule neurons maintained in vitro in the presence of a medium containing 25 mM K+ (differentiating condition) or 5 mM K+ (pro-apoptotic condition), and determined the effect of culture medium, TGF-beta1 and IGF-1 on THG-1pit expression and intracellular localization. Thg-1pit encoded a 42 kDa MW protein and other, higher MW and developmentally-regulated forms. Cell exposure to 5 mM K+ elicited early and/or late waves of Thg-1pit transcription, depending on the presence/absence of TGF-beta1, and caused THG-1pit to massively and transiently move from cytoplasm and neurites to the nucleus. THG-1pit nuclear entrance was concomitant to that of AIF, suggesting that THG-1pit is involved in the induction of granule neuron apoptosis.