Autoimmune diseases currently impact over 250 million people globally. Current therapeutics typically provide symptomatic relief or halt progression temporarily, but significant side effects and relapses are still enormous challenges for autoimmune patients. Previous studies have shown that upregulation of the voltage-gated potassium channel Kv1.3 in effector memory T cells is associated with the pathogenesis of several autoimmune diseases (1-3). HsTX1[R14A] (MW 3741 Da) is a 34-residue disulfide-stabilised peptide that has picomolar potency and selectivity for Kv1.3 and has been shown to be effective in a rodent model of rheumatoid arthritis (4). However, like most peptides, HsTX1[R14A] is limited by rapid clearance, a short plasma half-life and non-targeted distribution which may result in more frequent dosing. Here we explored how lipid conjugation on HsTX1[R14A] affected the duration of circulation time and the distribution in organs and draining lymph nodes. HsTX1[R14A] was conjugated to lipids with various acyl chain lengths for pharmacokinetic studies, and Cy5 was conjugated to native and lipidated peptides for biodistribution studies (5). LCMS/MS assays were developed to quantify the lipidated peptides in mouse plasma. Conjugation of acyl lipids to HsTX1[R14A] was found to extend its exposure in plasma and tissues after subcutaneous injection in mice at 2 mg/kg. Biodistribution studies using Cy5-labelled lipidated HsTX1[R14A] demonstrated enhanced exposure in vital organs and at the injection site at 4 h after subcutaneous injection (2 mg/kg). Cy5-labelled lipidated HsTX1[R14A] was also found to have increased accumulation in the liver compared to HsTX1[R14A] while having significantly less exposure in the kidneys at 4 h after subcutaneous administration. Overall lipidation of HsTX1[R14A] is a promising method to optimise its therapeutic potential by extending tissue exposure.