The Ets transcription factor family is comprised of DNA-binding proteins that influence lymphoid development and activity and bind the consensus DNA site GGA(A/T) through a unique winged helix-turn-helix motif known as the Ets domain. Spi-B and Spi-C (also known as SPIC) are closely related Ets family members which share a conserved divergent sequence within the Ets domain that enables their binding to non-canonical AGAA sites. Spi-C is a 248 amino acid protein that localizes to the nucleus and, like other Ets family members, binds DNA as a monomer and plays a role in transcriptional regulation. Addi- tionally, Spi-C is thought to control the development of red pulp macrophages, thereby contributing to iron homeostasis and red blood cell recycling. Human Spi-C shares 65% amino acid identity with its mouse counterpart, suggesting a conserved role between species.