PITH domain-containing protein 1 (PITHD1)

PITH domain-containing protein 1 (PITHD1) is a conserved protein found in mammals, characterized by a PITH domain with a jelly roll β-sandwich fold. While structurally similar to the thioredoxin family, PITHD1 lacks the canonical dithiol CXXC motif and does not function as a classic redox enzyme. Functionally, it regulates cellular processes mostly through modulation of transcription and translation, notably activating the internal ribosomal entry site (IRES) to enhance RUNX1 gene expression, thereby promoting megakaryocyte differentiation and normal hematopoiesis. PITHD1 is expressed broadly but is notably upregulated in the olfactory tract in Alzheimer’s disease and downregulated in leukemia, implicating it in neurodegenerative and hematological diseases. In olfactory neuroepithelial cells, PITHD1 alters proliferation rates and triggers pro-inflammatory cytokine secretion, influencing pathways such as JAK-STAT and interleukin signaling. No direct drugs or inhibitors against PITHD1 are reported in the literature, and its therapeutic targeting remains unexplored. It is detected in multiple tissues and body fluids, acts in chromatin organization and signal transduction, and may function as a biomarker for Alzheimer’s disease and cancer progression.

Other names

C1orf128AD039HT014PP603TXNL1CLTXNL1 C-terminal likePITH (C-terminal proteasome-interacting domain of thioredoxin-like) domain containing 1

Not applicable; no PITHD1-targeting drugs reported. Mechanistically, enhances RUNX1 expression via activation of IRES and transcriptional upregulation