2D gel electrophoresis appears to be the most efficient way of analyzing and identifying the proteins. The rapid developments in the field of mass spectrometry have transformed it into a key technology in proteome research. The role of brain proteins in pathological and normal conditions has been a challenge for decades. The present work is aimed to investigate the brain expression proteomics and an initiative to construct a human brain regional protein profile that will support the elucidation of proteins involved in the diseased states. This paper discusses the human brain protein expression using 2 DE at narrow pI ranges, providing comprehensive information of the expressed proteins, helpful in elucidating the functional roles of various unidentified proteins. Such kind of significant data will lend a hand in exploring the complex mechanisms of neurological and neurodegenerative disorders.