The former San Francisco 49er superstar has unveiled the ad on Twitter.
Nike announced that Kaepernick will be a major part of its 30th anniversary "Just Do It" campaign.
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The campaign featuring the former 49er reads: "Believe in something, even if it means sacrificing everything," alluding to his kneeling protest over social injustice.
A giant billboard featuring Kaepernick has been placed prominently on top of Nike's flagship just off Union Square in San Francisco.
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Nike stocks rebounded a bit Wednesday morning following a dramatic dip after the announcement of the campaign.