We describe here LOTUS, a hitherto uncharacterized small globular domain, which was identified using sensitive sequence profile analysis. The LOTUS domain is found in germline-specific proteins that are present in the nuage/polar granules of germ cells. TDRD5 and TDRD7, two mammalian members of the germline Tudor group, possess three copies of the LOTUS domain in their extreme N-termini. The Tudor domains of these proteins bind symmetric dimethyl arginines present on the germ cell-specific Piwi proteins, which form a particular clade of Argonaute proteins. Piwi proteins interact with a specific class of non-coding RNAs [piwi-interacting RNAs (piRNAs)] and play a key role in the repression (silencing) of transposons and possibly other germline-specific functions. A LOTUS domain is also present in the Oskar protein, a critical component of the pole plasm in the Drosophila oocyte, which is required for germ cell formation. LOTUS domains are found in various proteins from metazoans and plants, are often associated with RNA-specific modules and are likely to adopt a winged helix fold. This suggests a germline-specific role in the mRNA localization and/or translation or a specific function toward piRNAs.