Bacteria localize proteins to distinct subcellular locations. One family of proteins with distinct cellular placement are chemoreceptors, which frequently localize to the bacterial pole. Although some polarity-promoting mechanisms have been described, there are many chemoreceptors that lack clear routes to becoming polar. The TlpD chemoreceptor ofHelicobacter pyloriis one such protein.H. pyloriis a chemotactic bacterial pathogen with four chemoreceptors. Its cytoplasmic chemoreceptor, TlpD, localizes to the pole in a manner that is independent of the other chemoreceptors. In this work, we evaluated the role of TlpD domains in its function. Truncated proteins were created that lacked different amounts of the N- or C-termini and expressed inH. pyloriin place of nativetlpDor as the sole chemoreceptor. These TlpD variants were examined for expression, protein localization, association with chemotaxis signaling proteins, and effect on motility. TlpD that lacked any portion of the N-terminal 104 amino acids did not produce detectable protein. In contrast, TlpD retained expression with loss of the C-terminal 45 amino acids. TlpD variants lacking the last 45 amino acids (TlpDΔC4) preserved the ability to interact with CheW and CheV proteins based on bacterial two-hybrid analysis but were unable to localize to the pole either on their own or in the presence of other chemoreceptors. TlpDΔC4 was found diffuse in the cytoplasm, and recruited detectable CheV1, CheV2, and CheV3 to this location but not CheW. TlpDΔC4 did not confer chemotactic abilities. These findings suggest the C-terminal end of TlpD plays a previously unappreciated role in promoting TlpD polar localization. The mechanism by which TlpD drives polar localization could translate to soluble cytoplasmic chemoreceptors in other bacterial pathogens.Author SummaryAlthough bacteria are small, they still place their proteins in specific locations that are required for the proteins to function. One such place is the bacterial end, or pole, where numerous proteins head to. How the bacterial cell identifies which proteins go to the pole is not fully understood. In this work, we dissect parts of a protein called TlpD that naturally goes to the pole. We find that mutants lacking one end of TlpD lose their polar placement. TlpD is part ofH. pylori’schemotaxis system, an ability that allows the bacteria to direct their motility towards beneficial situations and away from harmful ones. This ability is critical for infection inH. pyloriand numerous other pathogens. When TlpD loses its polar placement, the protein no longer functions, laying the foundation for future studies that can translate into therapies to treat or preventH. pyloriinfection.